Aydan Szeto

I started my lab in 2025 at WashU Pathology and Immunology to study the fundamental biology of type-2 immunity (how when it misbehaves leads to allergy), and how we might even turn it on its head to exploit this type of immune response to treat autoimmune inflammation. And now you’re thinking… what? How? Why?

The Yin and Yang of immunity

The immune system is all about balance, like a Yin Yang symbol ☯️. Actually technically it’s more like a three-way Yin Yang (Yong?) with a central ring that suppresses everything else, but lets stick with the simpler analogy here. The point is that different flavors of inflammation (how the immune system works) counter-balance each other. When our body is in healthy homeostasis, the different flavours are in harmony, and we feel great. But when one flavour tips over and dominate the response, that’s when we get immune diseases like autoimmunity (multiple sclerosis, IBD, autoimmune arthritis, psoriasis) and/or allergy (hay fever, asthma, atopic dermatitis/eczema). Isn’t it ironic that the immune system that’s supposed to protect us from bugs and pathogens is actually causing us harm? We still don’t fully understand why we develop these diseases, but we suspect that the industrialised environment over the past few decades may have played a role.

The immune system is everywhere

The other thing about our immune system is that it’s basically everywhere. All of our different organs and tissues have their unique make-up of immune cells that set up their inflammation tone. When this is disrupted in the gut - you get IBD! When this manifests in the skin - you can psoriasis! In fact the immune system is so important that it’s got something to do with how we age. As our body becomes older it becomes more pro-inflammatory, towards the type-1/17 kind (trying not to be too technical here…). This doesn’t help with autoimmune diseases as they are also driven by the same type-1/17 inflammation. With the increasing incidence of autoimmune diseases, compounded with our ageing population, this doesn’t look too good! ☄️

Harnessing the power of type-2 immunity

Because of the counter-regulatory nature of the immune system, when type-2 inflammation goes up, type-1/17 goes down. What if we can exploit this to dampen autoimmune and ageing-related (type-1/17) inflammation? 🧯 Here I believe in the potential of group 2 innate lymphoid cells (ILC2s), a weird and enigmatic cell type that was only discovered 15 years ago. They are kind of like the much more well known T cells, but ILC2s behave in a way that is not restricted by the limitations with T cells. For example, a person can only receive T cells derived from themselves because T cells from other people would attack them, unless you engineer them to “lose their identity”. So T cell therapies would typically be bespoke and very expensive. ILC2s, on the other hand, can be potentially universal and off-the-shelf. ILC2s can also multiply tremendously to get to the numbers we need for the purpose of cellular therapy.

So what’s the catch?

If this sounds too good to be true, that’s because it is! ILC2s drive type-2 immunity, which itself is associated with allergic responses 🤧. The last thing we want is to get rid of autoimmune symptoms only to be stuck with a new allergy! This is where innovation is needed and our work comes in. The Szeto lab will explore how modifying ILC2s with synthetic elements to endow them with favouable properties can unleash their power in modifying tissue inflammation, and more importantly, in a safe and effective way. Our goal is to innovate a whole new class of therapeutic immune cell to address a global health burden 🩺.

Focus on fundamental science

Although I firmly believe in the therapeutic potential of ILC2s to make a significant impact on human health, my own background in scientific research has deep roots in fundamental discovery of basic biology. There is still so much we don’t know about how type-2 immunity is regulated, and I am really excited to build on my previous work on CRISPR screens, Boolean gene circuitry and the “type-2 niche” to make more discoveries at WashU. I also believe this type of “high-throughput” approach will help us make ILC2s better cellular medicines, linking back to our top aim!

Get in touch!

If this sounds interesting to you and you want to get involved, drop me an email! You’ll know where to find it if you’re not a bot. 📧